Prostaglandins hydrogenation

The (dextrorotatory) 11,15-bis-THP ether of PGp2a was also transformed into prostaglandins of the first series by selective hydrogenation of the Z-A bond (Ref. 3). 

A formal total synthesis of the prostaglandin involved unmasking of an isoxazoline ring by hydrogenation over W-2 Raney Ni/BCl3/MeOH, H2O to reveal a -hydroxyketone. It was necessary in this case to deactivate the Raney... 

Following the initial abstraction of a hydrogen atom, the carbon radical then reacts with 02 to give an oxygen radical, which reacts with aC C bond within the same molecule in an addition reaction. Several further transformations ultimately yield prostaglandin H2. 

M., Humphrey, G.R. et al. on the long term factory process for the production of a prostaglandin D2 receptor antagonist - unprecedented asymmetric hydrogenation of an indole Fxo-Cyclic Trisubstituted a,(i-Unsaturated Acid. 

Many hormones and other blood-borne substances (including drugs) also alter contractile activity of smooth muscle. Some of the more important substances include epinephrine norepinephrine angiotensin II vasopressin oxytocin and histamine. Locally produced substances that may alter contraction in the tissue in which they are synthesized include nitric oxide prostaglandins leukotrienes carbon dioxide and hydrogen ion. 

Similar to LOXs, cyclooxygenases may catalyze superoxide production in the presence of NADH and NADPH [49]. It has been shown [88] that prostaglandin H synthase produced oxygen radicals and hydrogen peroxide during the transformation of 2(3)-tcrt-butyl-4-... 

The prostaglandin Ei and E2 analogues showing antisecretory and cytoprotective activities49,50 had to be deuterium or tritium labelled for preclinical studies. The tritiated or deuteriated title compounds 61, 62 and 63 have been synthesized51 by the methods outlined in equations 25, 26 and 27. Compounds 61 and 62, with hydrogen at 7-position... 

An important example of heterogeneous diastereoselective synthesis by catalytic way is the synthesis of prostaglandines (a family of compounds having the 20-carbon skeleton of the prostanoic acid) (Scheme 14.14). Naturally, these molecules are biosynthesized via a cyclooxygenase enzyme system that is widely distributed in mammalian tissues. Many of the synthetic routes [272] involve the diastereoselective hydrogenation of a carbonylic bond having a C=C double bond... 

Scheme 14.14 Possible routes in hydrogenation of a prostaglandin intermediate.

For an organism to eliminate a lipophilic, chemically inert xenobiotic, it is usually hrst necessary to oxidize it to a more polar form. In addition, many biosynthetic pathways that produce steroid hormones, prostaglandins, leukotrienes, etc. involve oxidative steps. Organisms have evolved many enzymes to carry out these oxidations. Oxidation can occur by addition of oxygen (without addition of hydrogen which would represent hydration), removal of hydrogen atoms (without removal of oxygen which would represent dehydration), or simply removal of electrons. 

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